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Biomedical subjects

A D Befus

Publications and source records attributed to A D Befus.

At least 145 records · Page 8Linked to original sources

Immediate IgA precursor cells in rabbit intestinal lamina propria.

Immunofluorscence studies have shown that injection of lymphocytes from either the intestinal lamina propria (LP) or from the Peyer's patches (PP) into irradiated (1000-1250 rad) allogeneic rabbits leads to the differentiation and proliferation of IgA containing cells in the spleen, mesenteric lymph node (MLN) and intestine by day 6 and to a lesser extent by day 4. In contrast, few IgA containing cells were seen in irradiated animals not given lymphocytes or given popliteal lymph node cells. Transfer of PP lymphocytes resulted in statistically greater numbers of IgA containing cells in the recipient MLN or spleen than did transfer of LP lymphocytes. In the PP of recipient rabbits given either LP or PP lymphocytes, intercellular IgA was abundant and more IgA containing cells were seen near the PP than in sites distant from PP. These results show that IgA precursor cells are present in the intestinal LP as well as in the PP. The nature and distribution of the IgA precursor and the characteristics of the IgA repopulation are discussed.

Animals↗

Possible immunological damage to the tegument of Hymenolepis diminuta in mice and rats.

Opaque or darkened areas (DA) of variable size and position occur on Hymenolepis diminuta in mice and rats. In mice DA normally first appear in the neck region of the worm but subsequently they appear elsewhere and increase in number until destrobilation or worm expulsion. The posterior of destrobilated worms is often darkened. In the more immunogenic infections with six cysticercoids there are more DA per worm than in infections with one cysticercoid. DA are areas of the tegument with a homogeneous increase in electron density; abnormal mitochondria; reduced granular endoplasmic reticulum, Golgi complexes and discoidal secretory bodies; and accumulation of lipid droplets. DA disappear from worms maintained for up to 4 h in Hanks' balanced salt solution and can be induced by mechanical damage to the worms. As the numbers of DA increase with the duration and intensity of infection and have similarities with types of cell injury, they are probably sites of worm pathology induced by host immunity.

Animals↗

Secondary infections of Hymenolepis diminuta in mice: effects of varying worm burdens in primary and secondary infections.

In one (1 c) and six (6 c) cysticercoid primary infections of Hymenolepis diminuta in NIH (inbred) and CFLP (outbred) male mice 6 +/- 1 weeks old greater than 85% of the worms established but were rejected (destrobilated or expelled) subsequently. Rejection occurs more quickly in 6 c infections than in 1 c infections. Considerable worm growth occurs in 1 c and 6 c primary infections but worms from 6 c infections weighed less than worms from 1 c infections on all days studied. Expulsion of H. diminuta does not occur more rapidly in secondary infections than in primary infections; loss of 6 c secondary worms occurs at the same rate as 6 c primary worms but 1 c secondary worms survive longer than 1 c primary worms. Although worms are not lost more quickly in secondary than in primary infections, they are affected at an early age by the immune response which stunts their growth. Increasing the intensity of primary and secondary infections increases the severity of stunting of secondary worms. The results are discussed and it is suggested that immune responses to Hymenolepis spp. in rodents are common but that thresholds of worm numbers exist below which appreciable worm loss does not occur. Stunting due to crowding, which generally is attributed to inter-worm competition, may be in part immunologically mediated. For future immunological studies attempting to induce secondary responses to H. diminuta in mice, worm growth, not survival, is the criterion to evaluate.

Animals↗

Tumour markers in the detection of opisthorchiasis-associated cholangiocarcinoma.

Opisthorchiasis is a major public health problem in north-east Thailand, where over 7 million inhabitants are reported to be infected. A significant percentage of infected individuals develops cholangiocarcinoma terminally, which is rapidly fatal. To determine whether certain tumour markers are elevated in Thai patients with cholangiocarcinoma, and thus might be useful in the diagnosis of cholangiocarcinoma associated with opisthorchiasis in Thailand, the tumour markers CA125 and CA19-9 were measured by radioimmunoassay in 94 serum samples. The subjects consisted of 52 patients admitted for non-gastroenterological diseases, 7 patients with histologically proven cholangiocarcinoma, 7 patients with clinically suspected cholangiocarcinoma, and 28 patients with uncomplicated opisthorchiasis. The mean levels (+/- standard deviation [SD]) of CA19-9 and CA125 in the controls were 12.5 +/- 10.2 and 24.7 +/- 11.1 units/ml respectively. Using the mean + 3SD as the cut-off level, 57.1% of patients with confirmed cholangiocarcinoma had elevated CA19-9 and 28.6% had elevated CA125. In patients with clinically suspected cholangiocarcinoma, 71.4% had elevated CA19-9 and 28.6% had elevated CA125. Among opisthorchiasis patients, 3.6% had elevated CA125 and none had elevated CA19-9. 1.9% of controls had elevated CA19-9 and none had elevated CA125. When positivity of either CA125 or CA19-9 was used as an indicator of malignancy, the sensitivity and specificity of the combined tests reached 85.7% and 98.1% respectively. These preliminary results suggest that the measurement of CA125 and CA19-9 may be useful in the early detection of opisthorchiasis-associated cholangiocarcinoma.

Adenoma, Bile Duct↗

Serum antibody response to Opisthorchis viverrini antigen as a marker for opisthorchiasis-associated cholangiocarcinoma.

The liver flukes Opisthorchis viverrini and Clonorchis sinensis chronically infect over 30 million people in south-eastern Asia, resulting in significant morbidity and a predisposition to cholangiocarcinoma (CCA). Liver fluke-associated CCA carries a poor prognosis, partly because it is often detected at a late and advanced stage. The development of improved diagnostic methods, particularly for early CCA, may improve chances of survival and cure. Accordingly, we explored the use of immunological responses to liver fluke antigens as a potential means of identifying individuals at high risk for liver fluke-associated CCA. Serum antibody responses to O. viverrini adult worm homogenate and metacercaria homogenate (MH) were studied using enzyme-linked immunosorbent and immunoblot assays in 65 infected residents of an opisthorchiasis-endemic area in Thailand. Antibody levels correlated with liver ultrasonography (U/S) findings, and immunoblot analysis revealed a 91/93 kDa MH doublet recognized only by sera of individuals with severe liver U/S findings, including CCA. These results suggest that serum antibody responses to liver fluke antigens may be useful in the identification of infected individuals who are at high risk for liver fluke-associated CCA.

Animals↗

The "Roaring Adventures of Puff": a childhood asthma education program.

The "Roaring Adventures of Puff" (RAP) is a childhood asthma education program that targets children 7 to 12 years of age and their families. This program is designed to improve the quality of life of these children and improve asthma management for optimal asthma control. The program uses interactive educational strategies based on the principles of the Social Cognitive Theory. The article highlights aspects of the theory, provides an overview of the RAP program, and outlines some of the practical components of the program. RAP is an innovative program that is adaptable to a variety of settings and may serve as a health education model for children.

Asthma↗

Factors associated with poor asthma control in children aged five to 13 years.

BACKGROUND: Most children with asthma should be able to achieve acceptable control. However, are there differences between those with acceptable and poor control, and if so, how can health care approaches be modified accordingly? OBJECTIVE: To examine the characteristics of elementary school children aged five to 13 years with acceptable and poor levels of asthma control. METHODS: The present cross-sectional study of children with asthma used five indicators of control, as outlined by the Canadian Asthma Consensus Report, to categorize acceptable and poor asthma control. RESULTS: Of 153 children, 115 (75%) were rated as having poorly controlled asthma. Of those with poor control, 65 (64%) children were currently using inhaled corticosteroids, and 65% of those reported using inhaled corticosteroids daily versus as needed. Fifty-one per cent of the children with poorly controlled asthma had exposure to tobacco smoke, whereas 79% of the children with asthma under acceptable control were from households with no smokers (P=0.002). The poor control group also had significantly worse parental perceptions of the psychosocial impact of asthma on their child. No significant difference was found in the percentage of those who had written action plans in the poor control group (28%) compared with the acceptable control group (26%), and similar percentages in each group stated that they used the plans. CONCLUSIONS: Despite the high use of inhaled corticosteroids, the majority of children had poorly controlled asthma. The poor control group had more exposure to tobacco smoke and a worse psychosocial impact due to asthma. Few children had past asthma education and action plans, suggesting that there is a need to improve access to and tools for education.

Administration, Inhalation↗

Novel CD8 molecule on macrophages and mast cells: expression, function and signaling.

BACKGROUND: We previously identified, using flow cytometry and in situ RT-PCR, a novel CD8 molecule on rat alveolar macrophages (AM) and mast cells (MC). RT-PCR also demonstrated that mouse AM express CD8 mRNA. Functional studies on rat AM determined that ligation of CD8 alpha- and beta-chains induced inducible nitric oxide synthase (iNOS) upregulation, nitric oxide (NO), TNF-alpha and IL-1beta (CD8alpha only) secretion. However, CD8 did not induce AM phagocytosis of IgG-opsonized or unopsonized particles. Rat MC stimulated through CD8 secreted NO and TNF-alpha, but not histamine. Because of its potential role in regulating cell function, we investigated the signaling pathways involved in macrophage CD8 stimulation. METHODS AND RESULTS: Inhibitor of src family kinases (PP1) significantly (p<0.05) inhibited CD8alpha (OX8 antibody)-induced iNOS upregulation, NO, TNF-alpha and IL-1beta production in rat AM. In addition, Ro 31-8220 (a PKC inhibitor) inhibited OX8-induced iNOS upregulation, NO and IL-1beta production, but did not inhibit TNF-alpha production. Using Syk antisense, we further determined that OX8 stimulation of NO is Syk kinase dependent. CONCLUSION: Studies on the signaling mechanisms of CD8 determined that src family kinases, PKC, and Syk kinase are involved in CD8 signaling. Additionally, CD8 may have differential signaling pathways, as an inhibitor to PKC downregulated OX8-induced IL-1beta, but not TNF-alpha release. Our studies demonstrate that AM CD8 is similar to T lymphocyte CD8 in that src kinases are involved in CD8-mediated signaling. However, p56(lck), which is expressed in T lymphocytes, has not been found in macrophages, suggesting that other src family kinases may be involved in AM and MC CD8 signaling.

Animals↗

Inhibition of allergic inflammation by C-terminal peptides of the prohormone submandibular rat 1 (SMR-1).

BACKGROUND: The C-terminal of the prohormone submandibular rat 1 protein (SMR-1) contains several small peptides that reduce the severity of allergic inflammation and septic shock, and are part of the cervical sympathetic trunk-submandibular gland (SMG) axis of neuroendocrine immunology. These peptides include the heptapeptide, submandibular gland peptide-T and the tripeptide FEG. The D-isomeric form of this tripeptide, feG, which is active when administered orally, reduces LPS-provoked leukocyte rolling on mesenteric venules and influx of inflammatory cells into the peritoneum and intestinal muscle. METHODS: To investigate the mechanism of action of these peptides, the influx of inflammatory molecules into the airways, and several properties of human neutrophils were examined. RESULTS: Oral feG (1 mg/kg) inhibited the influx of inflammatory cells into the airways lumen of allergen challenged, sensitized Brown Norway rats. This inhibition occurred whether feG was given 30 min prior to 6 h post allergen challenge. Moreover, feG in picomolar to nanomolar concentrations inhibited PAF elicited chemotaxis by 30-40%, but the peptides did not affect superoxide production or phagocytosis by neutrophils. feG reduced PAF-stimulated expression of CD11b. CONCLUSIONS: feG may exert its anti-inflammatory effects by modulating the expression and functions of beta(2) integrins. The CST-SMG axis may be a major neuroendocrine pathway that modulates allergic asthma and other inflammatory responses.

Allergens↗

Interferon and antiallergic drug regulation of histamine and tumor necrosis factor-alpha in rat mast cell subsets.

We have further characterized the heterogeneity of mast cells (MCs) by comparing the ability of rat peritoneal MCs (PMCs) and intestinal mucosal MCs (IMMCs) to produce tumor necrosis factor (TNF)-alpha and by investigating its regulation by interferon (IFN) and the antiallergic drugs nedocromil sodium (NED) and sodium cromoglycate (SCG). Although IMMCs store less TNF-alpha than PMCs, they produced comparable amounts of TNF-alpha in cytotoxic assays. Just as SCG and NED inhibit histamine secretion from PMCs but not IMMCs, IFN exhibited a similar differential effect on histamine release from these cells. However, SCG, NED, and IFN inhibit TNF-alpha-dependent cytotoxicity by both PMCs and IMMCs and reduce the steady-state levels of mRNA for TNF-alpha in PMCs. Thus, the modulation of MC mediator release depends upon the MC population and mediator studied. The inhibitory effect of SCG and NED on TNF-alpha release from MCs may explain some of their anti-inflammatory and therapeutic effects.

Animals↗